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We developed a novel quantification method named "shape feature" by combining the features of amyloid positron emission tomography (PET) and brain magnetic resonance imaging (MRI) and evaluated its significance in predicting the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. From the ADNI database, 334 patients with MCI were included. The brain amyloid smoothing score (AV45_BASS) and brain atrophy index (MR_BAI) were calculated using the surface area and volume of the region of interest in AV45 PET and MRI. During the 48-month follow-up period, 108 (32.3%) patients converted from MCI to AD. Age, Mini-Mental State Examination (MMSE), cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), apolipoprotein E (APOE), standardized uptake value ratio (SUVR), AV45_BASS, MR_BAI, and shape feature were significantly different between converters and non-converters. Univariate analysis showed that age, MMSE, ADAS-cog, APOE, SUVR, AV45_BASS, MR_BAI, and shape feature were correlated with the conversion to AD. In multivariate analyses, high shape feature, SUVR, and ADAS-cog values were associated with an increased risk of conversion to AD. In patients with MCI in the ADNI cohort, our quantification method was the strongest prognostic factor for predicting their conversion to AD. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is one of the most common neurodegenerative diseases caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD is still unclear, the death of dopaminergic neurons during PD progression was revealed to be associated with abnormal aggregation of α-synuclein, elevation of oxidative stress, dysfunction of mitochondrial functions, and increased neuroinflammation. In this study, the effects of Licochalcone D (LCD) on MG132-induced neurotoxicity in primitive neural stem cells (pNSCs) derived from reprogrammed iPSCs were investigated. A cell viability assay showed that LCD had anti-apoptotic properties in MG132-induced oxidative-stressed pNSCs. It was confirmed that apoptosis was reduced in pNSCs treated with LCD through 7-AAD/Annexin Ⅴ staining and cleaved caspase3. These effects of LCD were mediated through an interaction with JunD and through the EGFR/AKT and JNK signaling pathways. These findings suggest that LCD could be a potential antioxidant reagent for preventing disease-related pathological phenotypes of PD. [ABSTRACT FROM AUTHOR]

A substantial amount of amyloid-beta (Aβ) accumulates in the occipital cortices; however, it draws less attention. We investigated the clinical implications of Aβ accumulation in the occipital lobes in the Alzheimer's disease (AD) continuum. [18F]-Florbetaben amyloid PET scans were performed in a total of 121 AD or amnestic mild cognitive impairment (aMCI) patients. Of the 121 patients, 74 Aβ positive patients were divided into occipital Aβ positive (OCC+) and occipital Aβ negative (OCC−) groups based on Aβ accumulation in the bilateral occipital lobes. The OCC+ group (41/74, 55.4%) was younger and had a younger age at onset than the OCC− group. The OCC+ group also had an increased standard uptake value ratio in the occipital lobes and greater cortical thinning in relevant areas. The OCC+ group had a higher global deterioration scale, lower performance for the copy, immediate recall, delayed recall, and recognition in Rey–Osterrieth Complex Figure tests than the OCC- group, although both groups had similar disease durations. AD or aMCI patients in the OCC+ group exhibited features noted in early onset AD with relevant neuropsychological and image findings. Occipital Aβ positivity in amyloid PET scans need to be considered as an underestimated marker of early onset AD continuum. [ABSTRACT FROM AUTHOR]

The recent advance of positron emission tomography (PET) tracers as biomarkers in Alzheimer's disease (AD) provides more insight into pathophysiology, preclinical diagnosis, and further therapeutic strategies. However, synergistic processes or interactions between amyloid and tau deposits are still poorly understood. To better understand their relationship in focal brain changes with clinical phenotypes, we focused on region-specific or atypical AD characterized by focal clinical presentations: Posterior cortical atrophy (PCA) and logopenic variant of primary progressive aphasia (lpvPPA). We compared three different PET images with 18F–THK–5351 (tau), 18F–Florbetaben (amyloid beta, Aβ), and 18F–Fluorodeoxyglucose (glucose metabolism) to investigate potential interactions among pathologies and clinical findings. Whereas the amyloid accumulations were widespread throughout the neocortex, tau retentions and glucose hypometabolism showed focal changes corresponding to the clinical features. The distinctly localized patterns were more prominent in tau PET imaging. These findings suggest that tau pathology correlates more closely to the clinical symptoms and the neurodegenerative processes than Aβ pathology in AD. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disease, causing movement defects. The incidence of PD is constantly increasing and this disease is still incurable. Thus, understanding PD pathophysiology would be pivotal for the development of PD therapy, and various PD models have thus been already developed. Through recent advances in reprogramming techniques, a primitive neural stem cell (pNSC) derived from PD patient induced pluripotent stem cells (iPSCs) could be potentially used as a reproducible and reliable experimental system to analyze the effect of the leucine-rich repeat kinase 2 G2019S mutation (LK2GS) in neural cells. Here, we investigated the advantages of such a model system through quantitative proteomic analysis of pNSCs from normal control iPSCs and familial PD patient iPSCs harboring LK2GS. We confirmed that the expression of molecules known to be involved in PD pathogenesis, such as oxidative stress-, cell adhesion-, and cytoskeleton-related proteins, were altered in the LK2GS pNSC. In addition, we showed that down-regulation of Ku80, which was found in the proteomic analysis with LK2GS pNSCs, resulted in apoptosis induced by DNA damage response. Taken together, we suggest that pNSCs from PD iPSCs could provide a reliable and useful model system to study PD. Moreover, the highly expandable pNSC is suitable for multi-omics approaches to understand PD pathologies and discover therapeutic targets for PD. [ABSTRACT FROM AUTHOR]

CXCL8 (interleukin-8, IL-8) is a CXC family chemokine that recruits specific target cells and mediates inflammation and wound healing. This study reports the identification and characterization of two cxcl8 homologs from rock bream, Oplegnathus fasciatus. Investigation of molecular signature, homology, phylogeny, and gene structure suggested that they belonged to lineages 1 (L1) and 3 (L3), and designated Ofcxcl8-L1 and Ofcxcl8-L3. While Ofcxcl8-L1 and Ofcxcl8-L3 revealed quadripartite and tripartite organization, in place of the mammalian ELR (Glu-Leu-Arg) motif, their peptides harbored EMH (Glu-Met-His) and NSH (Asn-Ser-His) motifs, respectively. Transcripts of Ofcxcl8s were constitutively detected by Quantitative Real-Time PCR (qPCR) in 11 tissues examined, however, at different levels. Ofcxcl8-L1 transcript robustly responded to treatments with stimulants, such as flagellin, concanavalin A, lipopolysaccharide, and poly(I:C), and pathogens, including Edwardsiella tarda, Streptococcus iniae, and rock bream iridovirus, when compared with Ofcxcl8-L3 mRNA. The differences in the putative promoter features may partly explain the differential transcriptional modulation of Ofcxcl8s. Purified recombinant OfCXCL8 (rOfCXCL8) proteins were used in in vitro chemotaxis and proliferation assays. Despite the lack of ELR motif, both rOfCXCL8s exhibited leukocyte chemotactic and proliferative functions, where the potency of rOfCXCL8-L1 was robust and significant compared to that of rOfCXCL8-L3. The results, taken together, are indicative of the crucial importance of Ofcxcl8s in inflammatory responses and immunoregulatory roles in rock bream immunity. [ABSTRACT FROM AUTHOR]